Hypothyroid with hyperthyroid symptoms

PMC

5. DISCUSSION

This case highlights the challenges of managing a patient with GD and spontaneously oscillating thyroid function, particularly given her reluctance to undergo definitive therapy.

The switching of hyperthyroidism to hypothyroidism is uncommon in GD and most episodes occur several years after the cessation of antithyroid medications.2 Comparably, the flipping of patients from hypothyroidism to hyperthyroidism is much rarer, with only 37 such cases reported in the literature by 2014.1 The presentation of alternating hyperthyroidism and hypothyroidism therefore is an even rarer phenomenon in GD, and is described in very few case reports.3, 4 A possible reason for why it is uncommonly encountered in clinical practice may be because many patients with GD are referred relatively early in their disease course for definitive treatment, such as total thyroidectomy or radioactive iodine, thus eliminating the possibility for spontaneous oscillation of thyroid function.

Previously, it was thought that people with GD only had stimulating TSH receptor antibodies. However, now it is increasingly recognized that both TSAb and TBAb can be produced concurrently in the same patient5; the presence of hyperthyroidism or hypothyroid may depend on the balance between stimulating and blocking antibodies.6 The phenomenon of TSH receptor antibody switching between stimulating and blocking is infrequent.4 In a large study by Takasu & Matsushita, who followed‐up patients over 10 years, found that among 34 hypothyroid patients with TBAb predominance, only two subjects later developed TSAb‐dominant hyperthyroidism. Out of 98 TSAb predominant hyperthyroidism, only two subjects later developed TBAb‐dominant hypothyroidism.7 In a recent publication where TSAb and TBAb were quantified with a reporter gene bioassay using Chinese hamster ovary cells, <1% (10/1079) patients with autoimmune thyroid disease which included Hashimoto’s thyroiditis and GD, were positive for both TSAb and TBAb.5

Unfortunately, we do not have the availability of TBAb measurement at our institution and only recently have been able to quantify TSAb. Monitoring of TRAb is important in pregnant women with GD, as TSAb and TBAb can cause neonatal thyrotoxicosis and hypothyroidism, respectively, and affect neonatal development.8 Thyroid peroxidase antibodies (TPO Ab), which are associated with Hashimoto’s thyroiditis, can exist in patients with GD. Although TPO Ab were not frequently requested in our case, the titer of TPO Ab increased during the hypothyroid phase. Hashimoto’s thyroiditis following Graves’ hyperthyroidism can occur, due to the expansion of autoantibody generation from TSH receptor initially to TPO subsequently,9 and change in balance between TSAb and TBAb.

There have been several theories put forth to account for the switching of TSAb and TBAb. Rarely, treatment with levothyroxine may increase thyroid autoantibody production including TSAb, such that hypothyroid patients can later become hyperthyroid.4 It is hypothesized that elevated thyroid hormone, through thyroxine replacement, affects the immune system such that it inhibits T regulatory cells and enhances expression of costimulatory molecules by dendritic cells, which are both important in antibody production and TSAb secretion.4 Treatment with antithyroid medications such as carbimazole reduces thyroid autoimmunity and TSAb secretion,10 and following treatment the balance could switch to predominately TBAb.

Autoimmune thyroid disease and oscillating thyroid function, similar to this case report, can occur following treatment with alemtuzumab for multiple sclerosis.11 Gilbert et al11 suggest that the switching of thyroid states following treatment with alemtuzumab was also likely due to change in balance between TSAb and TBAb. In addition, switching of thyroid autoantibodies has been found to occur more frequently in certain demographic groups including women, patients aged between 39 and 44 and those of Japanese background.4

An unconventional form of thyroid hormone replacement therapy, namely thyroid extract, was used in this case. Although it contains iodine, this is unlikely to have contributed to the flipping of hypothyroidism to hyperthyroidism in this case. Teng et al12 found that iodine supplementation in their study did not increase the incidence of GD or hyperthyroidism. Rather they found that high iodine intake was associated with autoimmune thyroiditis causing hypothyroidism.

Due to the unpredictable nature of the disease in patients with alternating hyperthyroidism and hypothyroidism, definitive therapy would be recommended to stabilize their thyroid hormone replacement in the long term. A block and replace regimen may improve stability over the short to intermediate term. Definitive therapy includes both thyroidectomy and radioactive iodine, which has the disadvantage in that it can only be performed in the hyperthyroid phase. Without definitive treatment, management can be challenging, and close monitoring of the patient along with regular thyroid function test will be required for ongoing follow‐up.13, 14

Conversion of autoimmune hypothyroidism to hyperthyroidism

  1. 1.

    Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA: The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977, 7: 481-493.

    • CAS
    • Article
    • Google Scholar
  2. 2.

    Canaris GJ, Manowitz NR, Mayor GM, Ridgway EC: The Colorado thyroid disease prevalence study. Arch Int Med. 2000, 160: 526-534.

    • CAS
    • Article
    • Google Scholar
  3. 3.

    Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE: Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002, 87: 489-499.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  4. 4.

    Jacobson EM, Tomer Y: The genetic basis of thyroid autoimmunity. Thyroid. 2007, 17: 1-13.

    • Article
    • Google Scholar
  5. 5.

    Tamai H, Kasagi K, Takaichi Y, Takamatsu J, Komaki G, Matsubayashi S, Konishi J, Kuma K, Kumagai LF, Nagataki S: Development of spontaneous hypothyroidism in patients with Graves’ disease treated with antithyroidal drugs: Clinical, immunological, and histological findings in 26 patients. J Clin Endocrinol Metab. 1989, 69: 49-53.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  6. 6.

    Takasu N, Yamada T, Sato A, Nakagawa M, Komiya I, Nagasawa Y, Asawa T: Graves’ disease following hypothyroidism due to hashimoto’s disease: studies of eight cases. Clin Endocrinol. 1990, 33 (6): 687-698.

    • CAS
    • Article
    • Google Scholar
  7. 7.

    Joplin GF, Fraser R: Thyrotoxicosis developing in recurrent nodular goitre with focal thyroiditis. Proc Roy Soc Med. 1959, 52: 177-178.

    • PubMed
    • CAS
    • PubMed Central
    • Google Scholar
  8. 8.

    Doniach D, Hudson RV, Roitt LM: Human autoimmune thyroiditis; Clinical studies. Brit Med J. 1960, 1 (5170): 365-373.

    • PubMed
    • CAS
    • PubMed Central
    • Article
    • Google Scholar
  9. 9.

    Gavras L, Thomson JA: Late thyrotoxicosis complicating autoimmune thyroiditts. Acta Endocrinol. 1972, 69: 44-46.

    • Google Scholar
  10. 10.

    Goolden AWG, Davidson M, Hoffenberg R: Myxedema preceding hyperthyroidism. Lancet. 1971, 2: 268-

    • PubMed
    • CAS
    • Article
    • Google Scholar
  11. 11.

    James KW: Myxedema preceding hyperthyroidism. Lancet. 1976, 2: 156-

    • Google Scholar
  12. 12.

    Bremner WJ, Griep RP: Graves’ thyrotoxicosis following primary thyroidal failure. J Am Med Assoc. 1976, 235: 1361-

    • CAS
    • Article
    • Google Scholar
  13. 13.

    Hochstein MA, Nair V, Nevins M: Hypothyroidism followed by hyperthyroidism. J Am Med Assoc. 1977, 237: 2222-

    • CAS
    • Article
    • Google Scholar
  14. 14.

    Bhandarkar S, Retnam V: Hyperthyroidism following hypothyroidism. J Postgrad Med. 1980, 26: 90-

    • PubMed
    • CAS
    • Google Scholar
  15. 15.

    Emil L, Robert EJ: Hypothyroid Grave’s Disease. South Med J. 1970, 90 (12): 1201-1203.

    • Google Scholar
  16. 16.

    Champion B, Gopinath B, Ma G, El-Kasissi S, Wall JR: Conversion to graves’ hyperthyroidism in a patient with hypothyroidism due to hashimoto’s thyroiditis documented by real-time thyroid ultrasonograpy. Thyroid. 2008, 18 (10): 1135-1137.

    • PubMed
    • Article
    • Google Scholar
  17. 17.

    Chung YH, Ou HY, Wu TJ: Development of hyperthyroidism following primary hypothyroidism: a case report. Kaohsiung J Med Sci. 2004, 20 (4): 188-191.

    • PubMed
    • Article
    • Google Scholar
  18. 18.

    Al-Sharafi BA, Khardori R: Hyperthyroidism after hypothyroidism. South Med J. 2000, 93 (7): 703-707.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  19. 19.

    Kohut WD, Gharib H, Anderson MW: Triiodothyronine thyrotoxicosis complicating primary hypothyroidism in a patient with autoimmune thyroiditis. Am J Med. 1982, 72 (5): 843-846.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  20. 20.

    Wakakuri N, Kubo T, Kitagawa M: Hyperthyroidism after primary hypothyroidism: Follow-up with serial thyroid biopsies. Arch Intern Med. 1985, 145 (8): 1527-1528.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  21. 21.

    Sung LC, McDougall IR: Graves’ hyperthyroidism: spontaneous occurrence after autoimmune hypothyroidism with persistent infiltrative ophthalmopathy. Arch Intern Med. 1978, 138 (6): 1009-1010.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  22. 22.

    Guansing AR, Klink DD, Engbring N: Graves’ disease following the occurrence of hypothyroidism. Henry Ford Hosp Med J. 1980, 28 (2–3): 152-157.

    • PubMed
    • CAS
    • Google Scholar
  23. 23.

    Skare S, Frey HMM, Konow-Thorsen R: Primary hypothyroidism followed by hyperthyroidism Five case reports. Acta Endocrinol. 1984, 105 (2): 179-183.

    • PubMed
    • CAS
    • Google Scholar
  24. 24.

    Steel NR, Bingle JP, Ramsay ID, Kendall-Taylor P: Myxoedema followed by TSAb-induced hyperthyroidism: report of 2 cases. Postgrad Med J. 1985, 61 (718): 717-720.

    • PubMed
    • CAS
    • PubMed Central
    • Article
    • Google Scholar
  25. 25.

    Perrild H, Hansen JM: Hypothyroidism followed by hyperthyroidism. Lancet. 1977, 2 (8048): 1129-

    • PubMed
    • CAS
    • Article
    • Google Scholar
  26. 26.

    Rivera JV, Reyes FM: Myxedema preceding thyrotoxicosis in Graves’ disease. Bol Asoc Med P R. 1968, 60 (9): 438-442.

    • PubMed
    • CAS
    • Google Scholar
  27. 27.

    Mäenpää J: Hypothyroidism preceding hyperthyroid Graves’ disease in two children. Acta Endocrinol. 1983, 251: 27-32.

    • Google Scholar
  28. 28.

    Fatourechi V, Gharib H: Hyperthyroidism following hypothyroidism: data on six cases. Arch Intern Med. 1988, 148 (4): 976-978.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  29. 29.

    McDermott MT, Kidd GS, Dodson LE, Hofeldt FD: Hyperthyroidism following hyperthyroidism. Am J Med Sci. 1986, 291 (3): 194-198.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  30. 30.

    Takeda K, Takamatsu J, Kasagi K, Sakane S, Ikegami Y, Isotani H, Majima T, Majima M, Kitaoka H, Iida Y: Development of hyperthyroidism following primary hypothyroidism: A case report with changes in thyroid related antibodies. Clin Endocrinol (Oxf). 1988, 28 (4): 341-344.

    • CAS
    • Article
    • Google Scholar
  31. 31.

    Olckzak S, MuCulloch AJ, Clark F: Thyrotoxic graves’ disease after Primary hypothyroidism. Br Med J. 1978, 2 (6138): 666-

    • Article
    • Google Scholar
  32. 32.

    Levine GA, Williams DE, Hershman JM, Beall GN: Graves hyperthyroidism following myxedema in a patient with recurrent carcinoma of the colon. West J Med. 1978, 128: 240-244.

    • PubMed
    • CAS
    • PubMed Central
    • Google Scholar
  33. 33.

    Bando Y, Nagai Y, Ushiogi Y, Toya D, Tanaka N: Development of Graves’ hyperthyroidism from primary hypothyroidism in a case of thyroid hemiagenesis. Thyroid. 1999, 9 (2): 183-187.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  34. 34.

    Ruchla M, Szczepanek E, Skiba A, Czepczynski R, Sowinski J: Graves’ hyperthyroidism following primary hypothyroidism due to hashimoto’s thyroiditis in a case of thyroid hemiagenesis: case report. Neuro Endocrinol Lett. 2008, 29 (1): 55-58.

    • Google Scholar
  35. 35.

    Takasu N, Yamashiro K, Ochi Y, Sato Y, Nagata A, Komiya I, Yoshimura H: TSBAb ( TSH- stimulation blocking antibody) and TSAb (thyroid stimulating antibody) in TSBAb-positive patients with hypothyroidism and Graves, patients with hyperthyroidism. Horm Metab Res. 2001, 33 (4): 232-237.

    • PubMed
    • CAS
    • Article
    • Google Scholar
  36. 36.

    Irvine WJ, Lamberg BA, Cullen D, Raud-Gordin R: Primary hypothyroidism preceding thyrotoxicosis. J Clin Lab Immunol. 1979, 8: 3-19.

    • Google Scholar

Hyperthyroidism
(Overactive)

No single treatment is best for all patients with hyperthyroidism. The appropriate choice of treatment will be influenced by your age, the type of hyperthyroidism that you have, the severity of your hyperthyroidism, other medical conditions that may be affecting your health, and your own preference. It may be a good idea to consult with an endocrinologist who is experienced in the treatment of hyperthyroid patients. If you are unconvinced or unclear about any thyroid treatment plan, a second opinion is a good idea.

Antithyroid Drugs: Drugs known as antithyroid agents—methimazole (Tapazole®) or in rare instances propylthiouracil (PTU)—may be prescribed if your doctor chooses to treat the hyperthyroidism by blocking the thyroid gland’s ability to make new thyroid hormone. Methimazole is presently the preferred one due to less severe side-effects. These drugs work well to control the overactive thyroid, and do not cause permanent damage to the thyroid gland. In about 20% to 30% of patients with Graves’ disease, treatment with antithyroid drugs for a period of 12 to 18 months will result in prolonged remission of the disease. For patients with toxic nodular or multinodular goiter, antithyroid drugs are sometimes used in preparation for either radioiodine treatment or surgery.

Antithyroid drugs cause allergic reactions in about 5% of patients who take them. Common minor reactions are red skin rashes, hives, and occasionally fever and joint pains. A rarer (occurring in 1 of 500 patients), but more serious side effect is a decrease in the number of white blood cells. Such a decrease can lower your resistance to infection. Very rarely, these white blood cells disappear completely, producing a condition known as agranulocytosis, a potentially fatal problem if a serious infection occurs. If you are taking one of these drugs and develop a fever or sore throat, you should stop the drug immediately and have a white blood cell count that day. Even if the drug has lowered your white blood cell count, the count will return to normal if the drug is stopped immediately. But if you continue to take one of these drugs in spite of a low white blood cell count, there is a risk of a more serious, even life-threatening infection. Liver damage is another very rare side effect. A very serious liver problem can occur with PTU use which is why this medication should not generally be prescribed. You should stop either methimazole or PTU and call your doctor if you develop yellow eyes, dark urine, severe fatigue, or abdominal pain.

Radioactive Iodine: Another way to treat hyperthyroidism is to damage or destroy the thyroid cells that make thyroid hormone. Because these cells need iodine to make thyroid hormone, they will take up any form of iodine in your bloodstream, whether it is radioactive or not. The radioactive iodine used in this treatment is administered by mouth, usually in a small capsule that is taken just once. once swallowed, the radioactive iodine gets into your bloodstream and quickly is taken up by the overactive thyroid cells. The radioactive iodine that is not taken up by the thyroid cells disappears from the body within days over a period of several weeks to several months (during which time drug treatment may be used to control hyperthyroid symptoms), radioactive iodine destroys the cells that have taken it up. The result is that the thyroid or thyroid nodules shrink in size, and the level of thyroid hormone in the blood returns to normal. Sometimes patients will remain hyperthyroid, but usually to a lesser degree than before. For them, a second radioiodine treatment can be given if needed. More often, hypothyroidism (an underactive thyroid) occurs after a few months and lasts lifelong, requiring treatment. In fact, when patients have Graves’ disease, a dose of radioactive iodine is chosen with the goal of making the patient hypothyroid so that the hyperthyroidism does not return in the future. Hypothyroidism can easily be treated with a thyroid hormone supplement taken once a day (see Hypothyroidism brochure).

Radioactive iodine has been used to treat patients for hyperthyroidism for over 60 years and has been shown to be generally safe. Importantly, there has been no clear increase in cancer in hyperthyroid patients that have been treated with radioactive iodine. As a result, in the United States more than 70% of adults who develop hyperthyroidism are treated with radioactive iodine. More and more children over the age of 5 are also being safely treated with radioiodine.

Surgery: Your hyperthyroidism can be permanently cured by surgical removal of all or most of your thyroid gland. This procedure is best performed by a surgeon who has experience in thyroid surgery. An operation could be risky unless your hyperthyroidism is first controlled by an antithyroid drug (see above) or a beta-blocking drug (see below), usually for some days before surgery, your surgeon may want you to take drops of nonradioactive iodine—either Lugol’s iodine or supersaturated potassium iodide (SSKI). This extra iodine reduces the blood supply to the thyroid gland and thus makes the surgery easier and safer. Although any surgery is risky, major complications of thyroid surgery occur rarely in patients operated on by an experienced thyroid surgeon. These complications include damage to the parathyroid glands that are next to the thyroid and control your body’s calcium levels (causing problems with low calcium levels) and damage to the nerves that control your vocal cords (causing you to have a hoarse voice).

After your thyroid gland is removed, the source of your hyperthyroidism is gone and you will become hypothyroid. As with hypothyroidism that develops after radioiodine treatment, your thyroid hormone levels can be restored to normal by treatment once a day with a thyroid hormone supplement.

Beta-Blockers: No matter which of these three methods of treatment are used for your hyperthyroidism, your physician may prescribe a class of drugs known as beta-blockers that block the action of thyroid hormone on your body. They usually make you feel better within hours to days, even though they do not change the high levels of thyroid hormone in your blood. These drugs may be extremely helpful in slowing down your heart rate and reducing the symptoms of palpitations, shakes, and nervousness until one of the other forms of treatment has a chance to take effect. Propranolol (Inderal®) was the first of these drugs to be developed. Some physicians now prefer related, but longer-acting beta-blocking drugs such as atenolol (Tenormin®), metoprolol (Lopressor®), nadolol (Corgard®), and Inderal-LA® because of their more convenient once- or twice-a-day dosage.

Endocrine Abstracts

Introduction: Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare although reported. We report a case of hypothyroidism that converted to a hyperthyroid state needing treatment.

Case report: A 36 years old female presented with a 3 months history of easy fatigability, cold intolerance, polymenorrhagia, constipation and weight gain. On examination she hadbradycardia and dry skin. Thyroid gland showed small diffuse enlargement. Clinical suspicion of primary hypothyroidism was made and thenconfirmed by TSH of >50 uIU/ml (0.4–4.2 uIU/ml) with FT4 value of <0.30 ng/dl and positive thyroid antibody titre. Thyroxine was started at 100 μg/day. Gradually requirement of thyroxine decreased and she maintained her TSH within normal range on 50 μg/day of thyroxine. After 3 years dose was further reduced to 25 μg/day but after 2 years again thyroxine dose was increased to 50 μg/day because of slightly increased TSH of 8.86. Slightly more than a year later she presented with weight loss of 3 kg and feeling of anxiety and tremors of hands. TSH was <0.005 with a FT4 of 2.4 confirming the state of thyrotoxicosis. Thyroxine was stopped and patient was observed over a period of 6 months. She remained clinically and biochemically hyperthyroid with a repeat TSH of <0.005 and FT4 of 2.66. Thyroid scintigraphy showed an increased homogenous tracer uptake. She was started on Carbimazoleand she remains on it till date.

Conclusion: This case demonstrate that high index of suspicion should be there if a patient with primary hypothyroidism develop persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

Living With Both Hypothyroidism and Hyperthyroidism

Imagine this scenario: You were feeling sluggish, packing on pounds, and your skin was dry.

Your doctor diagnosed you with hypothyroidism, which means you had an underactive thyroid gland. You began treatment and soon were feeling like yourself again.

Then, all of a sudden, you began to feel shaky and nervous and were losing weight despite all that you were eating — classic signs of hyperthyroidism, an overactive thyroid.

What gives?

Your thyroid, the butterfly-shaped gland located in the lower front of your neck, is tasked with making thyroid hormones that do everything from helping the body use energy and stay warm to keeping the brain, heart, muscles, and other organs functioning optimally.

It might seem counterintuitive at first glance, but some people can have both an underactive thyroid gland and an overactive one at different times in their life. And thought it’s rare to have both thyroid conditions, it’s far from impossible. Here’s what you need to know.

Scenario 1: Treatment-Induced Hypothyroidism to Hyperthyroidism, or Vice Versa

“Sometimes a person has hypothyroidism and is treated with too much thyroid hormone and may start to develop symptoms of hyperthyroidism, such as weight loss, rapid heart beat, sweatiness, and shakiness,” explains Minisha Sood, MD, an endocrinologist at Lenox Hill Hospital in New York City.

On the flip side, if you have hyperthyroidism and are treated aggressively with surgery and radiation, you could develop hypothyroidism, says David W. Lam, MD, an instructor in the division of endocrinology, diabetes, and bone diseases at Mount Sinai School of Medicine in New York City.

Scenario 2: Autoimmune-Mediated Hypothyroidism to Hyperthyroidism, or Vice Versa

Both hypothyroidism and hyperthyroidism can be caused by autoimmune diseases, which occur when your body’s immune system misfires against its own organs, including the thyroid. Symptoms wax and wane based on the type of antibodies that your body develops, Dr. Sood says. Some antibodies may indicate Grave’s disease (a form of hyperthyroidism), but over time the antibodies may trigger Hashimoto thyroiditis (a form of hypothyroidism).

“It is definitely possible,” says Dr. Lam. “The most common forms of hyperthyroidism and hypothyroidism are autoimmune-mediated.”

They can’t occur as co-morbidities, or at the same time, but they can occur in the same person over the course of his or her lifetime, he explains.

Recognizing Thyroid Conditions

How can you tell if one of these scenarios is happening to you? The answer, Sood suggests, is through frequent thyroid monitoring and getting smart about thyroid issues.

“We don’t want to box a patient into one diagnosis,” she says. “It’s important to know that it is possible to have features of both and that you may not fit into one classic scenario.”

As part of this ongoing conversation, Sood tells her patients who have hypothyroidism what it feels like if they have excessive medication in their system or if their stimulating antibodies are taking over and making too much thyroid hormone. She also tells hyperthyroid patients what it feels like to become hypothyroid so they know what to look for. Those symptoms may include dry skin, unexplained weight gain, thinning hair, and sluggish heart rate, she says.

“Keep a symptom diary, because sometimes symptoms can fluctuate so rapidly in such an unclear way that you may have a hard time keeping track otherwise,” she says.

However, Lam says there’s one hallmark characteristic that suggests you are switching from one to the other: “If you notice that your heart palpitations and tremors are gone and now you feel slow, your disease may be changing.” Most importantly, if you have one thyroid disorder, make sure to get routine medical care because it can transition between one and the other. And, he says, “we want to try to catch it early before it becomes flagrant.”

Oscillating Hypothyroidism and Hyperthyroidism: A Rare Autoimmune Syndrome

Gabriel Melkia, b, FNU Komala, Linda Lahama, Gres Karima, Vinod Kumara, Sushant Nanavatia, Mourad Ismaila

aDepartment of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ 07503, USA
bCorresponding Author: Gabriel Melki, Department of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ 07503, USA

Manuscript submitted May 28, 2019, accepted June 8, 2019
Short title: Oscillating Hypothyroidism and Hyperthyroidism
doi: https://doi.org/10.14740/jem583

  • Abstract
  • Introduction
  • Case Report
  • Discussion
Abstract ▴Top

Graves’ disease is an autoimmune thyroid disorder with overproduction of thyroid hormones secondary to the production of thyroid-stimulating hormone receptor (TSH-R) stimulating antibodies (TSAbs). It is very common for Graves’ disease patients to convert to a hypothyroid state especially in end-stage Graves’ disease or after iodine ablation. These patients require lifelong thyroxin replacement therapy. In this case report, we describe a rare phenomenon known as “oscillating hypo- and hyperthyroidism”. In this rare entity of autoimmune endocrine disorder patients with hypothyroidism spontaneously convert to Graves’ disease.

Keywords: Graves’ disease; Autoimmune; Oscillating hypothyroidism and hyperthyroidism; Oscillating hypo- and hyperthyroidism

Introduction ▴Top

Autoimmune thyroid diseases tend to move thyroid hormones in one direction. Graves’ disease is a well known cause for hyperthyroidism. While transforming from Graves’ hyperthyroidism into hypothyroidism is not uncommon, having both conditions simultaneously forms a unique combination and a challenge to medical management. We present a case of a 37-year-old woman who had oscillating hypothyroidism and hyperthyroidism, and a surgical ablation of the gland was recommended as definitive treatment.

Case Report ▴Top

A 37-year-old woman with the PMH of type 1 diabetes, Hashimoto thyroiditis being treated with levothyroxine and autoimmune pancreatitis came to the emergency department (ED) with complaints of palpitations, tremors, and anxiety. The patient’s vitals were: heart rate (HR): 110, temperature: 100 F, respiratory rate (RR): 18/min, blood pressure (BP): 160/90. Physical exam was positive for exophthalmos and pretibial myxedema. Patient labs revealed: high free T3 of 4.83 pg/mL and high free T4 of 2.18 ng/dL and undetectable thyroid-stimulating hormone (TSH) of 0.015 uIU/mL (Supplementary 1). Thyroid ultrasound revealed diffuse enlargement of the thyroid gland and thyroid isotope scan revealed diffusely increased uptake, suggestive of Graves’ disease and therefore TSH receptor (TSH-R) stimulating antibodies (TSAbs) were ordered which were positive.

Prior records of this patient revealed that the patient’s TSH was high (57.143 uIU/mL), free T3 (2.12 pg/mL) and free T4 (0.42 ng/dL) were low and patient was being treated with levothyroxine, but based on new signs and symptoms and new investigation the patient was diagnosed with Graves’ disease. Patient was offered various treatment options like thyroid ablation and surgery; however she refused any kind of intervention and was treated with methimazole.

After a few months, the patient developed signs and symptoms of hypothyroidism. Labs were drawn and revealed that the TSH was elevated at 62.993 uIU/mL, free T3 and free T4 were low at 2.01 pg/mL and 0.7 ng/dL respectively and TSH-R blocking antibodies (TBAbs) were sent and were positive. These symptoms and laboratory data were suspicious of hypothyroidism. The patient’s change from hyper- to hypothyroidism prompted us to diagnose the patient with oscillating hypothyroidism and hyperthyroidism.

Discussion ▴Top

Oscillating hypothyroidism and hyperthyroidism is an autoimmune entity due to the production of two types of thyrotropin receptor (TSH-R) autoantibodies found in immune disorders of the thyroid: TSAb and TBAb. TSAb is responsible for overactive thyroid gland causing Graves’s disease, while TBAb causes hypothyroidism by blocking endogenous TSH.

In one study by Takeda et al , they described that both types of TSH-R antibodies can coexist in one patient and that the thyroid function and clinical picture may change according to the balance of the type antibodies seen in the patient’s system.

In another study by McLachlan et al , they concluded that the balance between TBAb and TSAb can be shifted because of treatment with thyroid hormone replacement therapy or antithyroid treatment. Both therapies can alter the level of thyroid antibodies and can easily swing balance from hypo- to hyperthyroidism and vice versa.

This disease is difficult to treat as treatment of hypothyroidism can lead to overactive hyperthyroid. A block and replace regimen may improve stability over the short to intermediate term, but this is not a definitive therapy and requires long-term close monitoring. Definitive therapy includes both thyroidectomy and radioactive iodine, which has the disadvantage in that it can only be performed in the hyperthyroid phase .

The patient was educated about all available treatment options; however, the patient refused thyroidectomy and opted for treatment with antithyroid medications. The patient was specifically treated with methimazole. Without definitive treatment such as surgery or thyroid ablation, management can be challenging and close monitoring of the patient along with regular thyroid function test will be required for ongoing follow-up .

Conclusions

Physicians encounter cases of both hypothyroidism and hyperthyroidism throughout their careers; however they should always remain attentive to both the patient’s symptoms and laboratory values as cases of oscillating hypo- and hyperthyroidism are rare but need strict rigorous monitoring. Physicians must be careful in treating these cases, as patients can easily switch between hypo- and hyperthyroid states. The learning points include: 1) Patients with these autoimmune phenomena should be monitored with TSAb and TBAb along with thyroid function tests; and 2) Definitive therapy for oscillating hypothyroid and hyperthyroid is thyroidectomy (during any state of disease) or radioactive iodine ablation, while the patient is in the hyperthyroid state.

Acknowledgments

We thank Dr. Patrick Michael, Program Director of the Internal Medicine Residency for his continuous support and guidance.

Financial Disclosure

No funding was provided to any of the authors.

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from the patient for this case report.

Author Contributions

All authors contributed to the revision and approval of the manuscript.

▴Top
  1. Takeda K, Takamatsu J, Kasagi K, Sakane S, Ikegami Y, Isotani H, Majima T, et al. Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies. Clin Endocrinol (Oxf). 1988;28(4):341-344.
    doi
  2. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23(1):14-24.
    doi pubmed
  3. Wong M, Inder WJ. Alternating hyperthyroidism and hypothyroidism in Graves’ disease. Clin Case Rep. 2018;6(9):1684-1688.
    doi pubmed

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal of Endocrinology and Metabolism is published by Elmer Press Inc.

Pendulum swings from hypo- to hyperthyroidism: thyrotoxicosis after severe hypothyroidism following neck irradiation in a patient with a history of Hodgkin’s lymphoma

A 27-year old female presented with clinical and biochemical thyrotoxicosis (TSH – 0.01 μIU/mL (ref. range: 0.27–4.2 μIU/mL); free thyroxine (FT4) – 1.58 ng/dL (ref. range 0.98–1.63 ng/dL); free triiodothyronine (FT3) – 4.56 pg/mL (ref. range 2.6–4.4 pg/mL). Clinical examination revealed tachycardia about 100 beats/min and no obvious goitre. Autoimmune profile was suggestive of Graves’ disease . The patient had a history of Hodgkin’s lymphoma, diagnosed and treated with chemo- and radiotherapy (including the neck) at the age of 18. At the age of 20 she developed severe hypothyroidism (TSH > 100 μIU/ml), though with high titres of both aTPO (150 IU/mL) and aTSHR (37.56 IU/mL) antibodies. Thyroid function tests normalised after treatment with L-thyroxine (100 μg o.d.). At the age of 26 she became “anxious” and experienced “heart palpitations”. She was found to have suppressed TSH, that remained suppressed even when the dose of L-thyroxine was reduced and then discontinued. After further four months she was found to have raised FT3 (see above). Thyroid scintigraphy revealed a normal and homogenous iodine uptake (41 %). The patient responded very well to treatment with low dose thiamazole (10 mg od, later 5 mg o.d.) that was discontinued after about 12 months. About a year later (while 16-week pregnant) she was off medication and had mild subclinical thyrotoxicosis (TSH – 0.035 μIU/mL, FT4 – 1.04 ng/dL, FT3 – 3.09 pg/mL) and raised aTSHR antibodies, albeit at lower titre than before (7.87 IU/L).

According to the literature data thyroid dysfunction is one of the most common abnormalities seen after radiotherapy for Hodgkin’s disease that includes the neck . Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, appears in 20–30 % patients who had therapeutic radiotherapy administered to the neck region, and this usually occurs within the first 5 years after therapy (peak 2–3 years after treatment) . Irradiation of the thyroid may also increase the risk of Graves’ disease (relative risk 7.2–20.4), or Graves’ ophthalmopathy, thyroiditis, benign adenomas and thyroid cancer. The aetiology of radiation-induced thyroid dysfunction includes vascular damage, parenchymal cell damage and auto-immune reactions . There are reports, that after neck irradiation Graves’ disease may develop in patients previously receiving thyroxine, and indeed 33 % of the patients with Graves’ hyperthyroidism had received thyroxine before its onset . Therefore thyroid hormone-replacement therapy in patients with hypothyroidism after irradiation of the neck does not eliminate risk of other thyroid abnormalities at a later date. According to some authors, thyroiditis observed in Hodgkin’s disease may be the result of immune regulation disorders in Hodgkin’s disease . Furthermore, a possibility of a change from hypo- to hyperthyroidism typical for Graves’ disease is has been known for some time , and was also confirmed in more recent publications .

Takeda et al. demonstrated, by measuring changes in cyclic AMP, that thyroid stimulating and thyroid blocking antibodies may coexist within the same patient and their relative activities may change over the course of the disease. Our case illustrates that after neck irradiation, severe hypothyroidism can be followed by thyrotoxicosis. It should be noted that in our patient, both during hypo and hyperthyroidism, aTSHR were elevated. There are two types of aTSHR: thyroid stimulating antibodies (TSAb) and TSH-stimulation blocking antibodies (TBAb). TBAb block TSH-stimulation of the thyroid and cause hypothyroidism. On the other hand, TSAb stimulate the thyroid and result in Graves’ hyperthyroidism. In our opinion, in this case there was a gradual switch from TBAb into TSAb.

In some patients, TSAb and hyperthyroidism develop unexpectedly after hypothyroidism that is caused by TBAb . Fan et al. described a case with documented cycles of hypothyroidism alternating with hyperthyroidism. Also, as mentioned above, some hypothyroid patients after irradiation of the neck, while treated for the Hodgkin’s disease, developed hyperthyroidism . A number of mechanisms may be involved in switching from TBAb to TSAb. Significantly, thyroxine treatment in some patients is associated with increase TSAb that – in extreme cases – might lead to development of hyperthyroidism in hypothyroid patients , though whether this was a case in our patient is speculative as neck irradiation per se is considered to be capable of influencing changes in patients’ immune status.

TSH receptor antibodies (TRAb) are autoantibodies directed against the TSH receptor, predominantly located on the thyroid epithelial cell surface. Two types of TSH receptor antibody have been found to exist in patients with autoimmune thyroid disease: thyroid stimulating antibodies (TSAb) and TSH-stimulation blocking antibodies (TSBAb). It has generally been felt that patients with positive TSAbs develop Graves’ hyperthyroidism and those with TSBAb antibodies develop hypothyroidism and there is no co-existent antibody state. Whilst rare, several case reports have highlighted however that a switch from TSAb to TSBAb predominance (and vice versa) can occur and consequently result in oscillation between clinical and biochemical hyper- and hypothyroidism.

We present the chronological events, including clinical history and biochemical results of 3 patients with fluctuating thyroid status and correlate this with the history of therapeutic interventions for their thyroid disease. All 3 patients had positive TRAb antibodies and similarly to other case reports in the literature, were all women and had comparable characteristics to other patients with autoimmune thyroid disease.

Studies have shown that in cases where there is a simultaneous presence of TSAb and TSBAb in vivo, the subsequent clinical state of the patient can be correlated with the relative concentrations and affinities of these antibodies at any one time. A recent review discusses the potential mechanisms involved in this immunological and clinical thyroid switching including the impact of levothyroxine, anti-thyroid drugs and physiological states such as pregnancy on thyroid status. We discuss the importance of this rare phenomenon including the need for careful patient monitoring and the implications for prognosis and options for definitive management.

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *